This project is the continuation of eight years of work directed toward the understanding of the mechanism and significance of the universal myocardial depression produced by inhalation anesthetics. In the coming year, we plan to study the new halogenated anesthetic, isoflurane (Forane) in acute and chronic dog preparations. In collaboration with the cardiac metabolism group at Penn State Medical Center, we will look at the effect of several anesthetics on intermediary lipid and carbohydrate metabolism in the normal and ischemic pig heart. Finally, we hope to study the effect of anesthetics on the function and metabolism of pigs with ischemic heart disease as a result of coronary atherosclerosis from a combination of diet and radiation. Although one of our basic research aims is the elucidation of the subcellular mechanism of the negative inotropic effects of anesthetics, we also hope to generate information which will be valuable in the clinical management of patients with ischemic heart disease. BIBLIOGRAPHIC REFERENCES: Brower, R.W., Merin, R.G. Effect of Halothane on Left Ventricular Function in Young Swine. Fed. Proc. 34:435, 1975 (Abs.) Merin, R.G., Kumazawa, T., Luka, N.L. Myocardial Function and Metabolism in the Conscious Dog and During Halothane Anesthesia, in press, Anesthesiology 1976.